Catching cancer

The rundown on a cancer that spreads through infection in dogs. Are we …

We've know for over 100 years that canine transmissible venereal tumor (CTVT, or Stickler's sarcoma) is a weird beast. In lab settings, cancer cells could be readily transplanted from one individual to another and it seems to spread by a number of forms of contact in the wild. Samples collected from a variety of geographic regions showed a common set of genetic characteristics, suggesting a single tumor origin. But doubts remained as to whether the tumor cells themselves could be transmitted among dogs, or if this might represent a common transformation route triggered by an infectious agent, such as a virus. But, earlier this year, researchers showed that a facial cancer affecting Tasmanian Devils could be spread via transfer of the tumor cells themselves when the creatures bit each other during fights. With those results and the completed dog genome in hand, researchers went back and reanalyzed the transmission of CTVT.

Using samples from five different continents, the researchers confirmed that all tumor samples had a specific genetic signature (a transposon insertion). But they went well beyond previous work. They looked at the MHC genes, which the immune system uses to discriminate between self and non-self. No matter what the tumor's host looked like, all tumor samples had the identical MHC genotype. Cluster analysis of genotypes from a number of genomic locations placed all tumor samples in a single cluster that was unrelated to the hosts. The conclusion: no matter what the dog's genetic content was, all the tumors were nearly identical genetically. The only way for this to happen was if the tumor did not arise from the host dog itself. CTVT must be a transmissible cancer. But nearly identical leaves enough room to figure a few things out about CTVT based on these differences. For one, there already seem to be two distinct populations of the tumor cells. For another, the tumor appears to have originated in wolves, probably somewhere less than 2,000 years ago.

So, the evidence is pretty compelling that these tumor cells have left their original host, with its finite life-span, behind. In doing so, it's picked up a number of major genomic arrangements, and adapted to evade the immune system by down-regulating its MHC genes. It's clearly no longer a dog in any sense of the word, and its lifestyle now resembles any number of independent parasitic organisms. Is it a new species? Personally, I'd say yes. If so, it came about via an event that looks nothing like a speciation as we generally understand it. Given that there's at least three examples of transmissible cancers in mammals now, it might be time to start thinking about what these things might look like once given more time to evolve. The authors suggest that, in the absence of an obvious way for these tumors to exchange genetic material, they'll eventually pick up enough harmful mutations to kill them off. I'm less convinced. Regardless, it may be that we can find more such infectious once we think about what to look for, or something we've seen already might have characteristics that suggest such an origin.